Abstract
Small nucleolar RNA host gene 12 (SNHG12), as one of the long non-coding RNAs (lncRNAs), plays an oncogenic role in various cancers, however, its role in the chemoresistance of non-small cell lung cancer (NSCLC) is unclear. In this study, we investigated the effect of SNHG12 on multidrug resistance (MDR) in NSCLC. The results showed that SNHG12 was high-expressed and miR-181a was low-expressed in NSCLC tumor tissues and cell lines. Knockdown of SNHG12 reversed the resistance to cisplatin, paclitaxel and gefitinib in A549/DDP, A549/PTX and PC9/AB2 cells through inducing cell apoptosis. Moreover, SNHG12 silencing suppressed MAPK1 and MAP2K1 expression by upregulating miR-181a, leading to inhibition of the MAPK/Slug pathway through decreasing phosphorylated MAPK1 (p-MAPK1), phosphorylated MAP2K1 (p-MAP2K1) and Slug levels. Furthermore, downregulation of SNHG12 enhanced the sensitivity of NSCLC cells to cisplatin in nude mice. Overall, our study is the first to identify a SNHG12-miR-181a-MAPK/Slug axis to elucidate in part how SNHG12 exert functions in NSCLC MDR, providing a novel therapeutic target to overcome MDR in NSCLC.
Highlights
Lung cancer is one of the most common malignancies, and is the most frequent cause of cancerrelated mortality accounting for an estimated 1.59 million deaths worldwide [1]
The results showed that Small nucleolar RNA host gene 12 (SNHG12) was high-expressed and miR-181a was low-expressed in non-small cell lung cancer (NSCLC) tumor tissues and cell lines
The level of SNHG12 and miR-181a was further determined in NSCLC cell lines A549 and its drug-resistant cell strains (A549/DDP and A549/ PTX), H1299 and its drug-resistant cell strains (H1299/ DDP and H1299/PTX), PC9 and its gefitinib-resistant cell strain PC9/AB2, H358 and its gefitinib-resistant cell strain H358/AB2, and immortalization of human bronchial epithelial cell line HBE. Quantitative real-time PCR (qRT-PCR) analysis revealed that SNHG12 expression (Figure 1C and 1D) was dramatically increased and miR-181a expression (Figure 1E and 1F) was remarkedly reduced in A549, H1299, PC9 and H358 cells when compared with HBE cells (Figure 1C-1F)
Summary
Lung cancer is one of the most common malignancies, and is the most frequent cause of cancerrelated mortality accounting for an estimated 1.59 million deaths worldwide [1]. Chemotherapy is regarded as a major supplementary therapy used to manage NSCLC following surgical operation. Chemotherapeutic agents such as cisplatin and paclitaxel, involved in platinum-based chemotherapy, and gefitinib, one of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), are first-line treatments for NSCLC. Certain patients gradually develop multidrug resistance (MDR), limiting the effectiveness of chemotherapy.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
